Thiazide Diuretics

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Abstract
The benzothiadiazine diuretics, of which chlorothiazide is the prototype (and which for this discussion has included the nonthiazide, chlorthalidone), proved to be among the most useful therapeutics available. As diuretics, these compounds are equally effective when given in optimal dosage, and, although less potent than organomercurials, the ease of administration, the rarity of important side effects, and a clinically useful natriuretic potency have made these agents the diuretic of choice in most diseases associated with fluid retention. These compounds appear to inhibit net Na reabsorption in the distal nephron, and effect a primary excretion of Na and Cl. The single most important complication of therapy with thiazides is a secondary kaliuresis and potassium depletion. This complication may be avoided by dietary supplementation or by the simultaneous administration of an aldosterone antagonist. Other clinical uses of the thiazides are found in the treatment of vasopressin-resistant diabetes insipidus where the agents produce antidiuresis apparently dependent upon modest sodium depletion; and in the treatment of arterial hypertension. The mechanism of the antihypertensive effect of these agents is not understood, but recent studies lend support to the concept that these agents have a direct effect on vascular resistance not dependent upon the production of natriuresis.